OP0205 Clinical and Preclinical Assessment of The Anti-MCAM Monoclonal Antibody PRX003, A Potential Novel Treatment for Th17-Mediated Inflammatory Diseases

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 134.2-134
Author(s):  
M. Koller ◽  
K. Flanagan ◽  
M. Skov ◽  
R. Goldblum ◽  
S.G. Griffith ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Inflammatory Diseases ◽  
Novel Treatment

scholarly journals Amino Terminal Recognition by a CCR6 Chemokine Receptor Antibody Blocks CCL20 Signaling and IL-17 Expression via β-arrestin

2021 ◽  
Author(s):  
Sara Gómez-Melero ◽  
Fé Isabel García-Maceira ◽  
Tania García-Maceira ◽  
Verónica Luna-Guerrero ◽  
Gracia Montero-Peñalvo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Chemokine Receptor ◽  
Th17 Cells ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Specific Binding ◽  
Isolation And Purification ◽  
Amino Terminal ◽  
Important Target

Abstract Background: CCR6 chemokine receptor is an important target in inflammatory diseases. Th17 cells express CCR6 and a number of inflammatory cytokines, including IL-17 and IL-22, which are involved in the propagation of inflammatory immune responses. CCR6 antagonist would be a potential treatment for inflammatory diseases such as psoriasis or rheumatoid arthritis. The aim of this study is to develop an antagonistic monoclonal antibody (mAb) against human CCR6 receptor (hCCR6).Results: We generate monoclonal antibodies against hCCR6 immunizing Balb/c mice with hCCR6 overexpressing cells. The antibodies were tested by flow cytometry for specific binding to hCCR6, cloned by limiting dilution and resulted in the isolation and purification monoclonal antibody 1C6. By ELISA and flow cytometry, was determined that the antibody obtained binds to hCCR6 N-terminal domain. The ability of 1C6 to neutralize hCCR6 signaling was tested and we determined that 1C6 antibody were able to block response in β-arrestin recruitment assay with IC50 10.23 nM, but did not inhibit calcium mobilization. In addition, we found in a chemotaxis assay that 1C6 reduces the migration of hCCR6 cells to their ligand CCL20. Finally, we determined by RT-qPCR that the expression of IL-17A in Th17 cells treated with 1C6 was inhibited.Conclusions: In the present study, we applied whole cell immunization for successfully obtain an antibody that is capable to neutralize hCCR6 signaling and to reduce hCCR6 cells migration and IL-17 expression. These results provide an efficient approach to obtain therapeutic potential antibodies in the treatment of CCR6-mediated inflammatory diseases.

scholarly journals Rituximab: a novel treatment for refractory Riedel’s thyroiditis

2018 ◽  
Vol 2018 ◽  
Author(s):  
Leanne Hunt ◽  
Barney Harrison ◽  
Matthew Bull ◽  
Tim Stephenson ◽  
Amit Allahabadia
Keyword(s):  
Monoclonal Antibody ◽  
Case Report ◽  
Rare Condition ◽  
List Type ◽  
Patient Case ◽  
Riedel’S Thyroiditis ◽  
Novel Treatment ◽  
Tender Mass ◽  
Learning Points ◽  
Riedel's Thyroiditis

Summary This case report reviews the rare condition of Riedel’s thyroiditis via a patient case. The report highlights the difficulties that one may encounter when managing such a case in regards to patient symptoms, side effects of medications and the relapsing nature of the condition. The case report also highlights novel treatment in the treatment of Riedel’s thyroiditis, rituximab, how this works and the resolution of symptoms that we have achieved with our patient on this treatment. Learning points: Riedel’s thyroiditis is characterised by chronic inflammation, which causes dense fibrosis in the thyroid gland. Riedel’s thyroiditis can present with neck pain, dysphagia and dyspnoea with a firm, non-tender mass found on examination. Riedel’s thyroiditis is part of the IgG4-related systemic disorders. Rituximab is a monoclonal antibody that works against the protein CD20.

scholarly journals Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti–HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (3) ◽  
pp. 321-327 ◽  
Author(s):  
Tamam Bakchoul ◽  
Andreas Greinacher ◽  
Ulrich J. Sachs ◽  
Annika Krautwurst ◽  
Harald Renz ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Igg Antibody ◽  
Platelet Destruction ◽  
Blocking Antibody ◽  
Novel Treatment ◽  
Key Points ◽  
Specific Igg ◽  
Alloimmune Thrombocytopenia ◽  
Glycan Modification

Key Points The study describes a potential novel treatment of fetal alloimmune thrombocytopenia by dissecting the effector activities of an epitope-specific IgG antibody. Neither the in vivo transplacental transport nor the inhibiting properties of the blocking antibody are impaired by the N-glycan modification.

The Monoclonal Antibody-defined CAR-3 Antigen is a Serological Marker Associated with Pancreatic Carcinoma

1988 ◽  
Vol 3 (1) ◽  
pp. 29-35 ◽  
Author(s):  
M. Prat ◽  
E. Medico ◽  
P. Piantino ◽  
S. Bretti ◽  
F.P. Rossini ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Pancreatitis ◽  
Inflammatory Diseases ◽  
High Specificity ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Breast Carcinomas ◽  
Chronic Inflammatory Diseases ◽  
Healthy Donors

The monoclonal antibody-defined CARS antigen is a new carcinoma associated marker which is expressed on a mucin-like molecule. Serum concentrations of CARS were assayed in 181 patients with carcinomas of different organs, 20 patients with non-carcinomatous malignancies, 123 patients with inflammatory diseases and 150 healthy controls. Serum levels of CARS were significantly increased in 51% of the patients with pancreatic carcinomas, in 60% of patients with biliary tract carcinomas and in about 15% of the patients with carcinomas of the digestive apparatus. Sera from patients with breast carcinomas were negative, as well as sera from patients with melanomas or sarcomas. CAR-3 values in samples from patients with chronic pancreatitis were constantly negative, as were samples from healthy donors. Significant concentrations of CAR-3 were detected in 20% of the sera from patients with acute pancreatitis and in 15% of the sera from patients with cirrhosis. Because of its high specificity for pancreatic carcinomas compared to chronic pancreatitis, CARS seems a promising marker for distinguishing between neoplastic and chronic inflammatory diseases of the pancreas, whose differential diagnosis is difficult.

scholarly journals Abstract 1154: DCLK1 monoclonal antibody-based CAR-T cells as novel treatment strategy against multiple myeloma

2019 ◽  
Author(s):  
Sripathi M. Sureban ◽  
Robert Berahovich ◽  
Hua Zhou ◽  
Shirley Xu ◽  
Lijun Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
T Cells ◽  
Treatment Strategy ◽  
Car T Cells ◽  
Novel Treatment ◽  
Car T

scholarly journals Preferential Binding of Anti-Neutrophil Cytoplasmic Antibodies to an Unexpected Epitope of a Chimeric Proteinase 3 Mutant

2019 ◽  
Author(s):  
Marta Casal Moura ◽  
Gwen E. Thompson ◽  
Darlene A. Nelson ◽  
Lynn A. Fussner ◽  
Amber M. Hummel ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Binding Sites ◽  
Granulomatosis With Polyangiitis ◽  
Antigen Binding ◽  
Proteinase 3 ◽  
Necrotizing Vasculitis ◽  
Novel Treatment ◽  
Preferential Binding ◽  
Major Antigen

AbstractProteinase 3 (PR3) is the major antigen for anti-neutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3-targeting ANCAs (PR3-ANCAs) recognize different epitopes on PR3 and are thought to be pathogenic for the development of the necrotizing vasculitis. To identify epitopes recognized by PR3-ANCAs, we pursued a strategy based on human-murine chimeric PR3 mutants. Interestingly, rather than observing reduced binding of PR3-ANCAs to Epitope 5 on a PR3 mutant (iHm5-Val103) with chimeric mutations in Epitope 5, we found substantially increased binding of the majority of PR3-ANCAs to iHm5-Val103 compared with the PR3 mutant (iPR3-Val103) clinically used to detect PR3-ANCAs. More interestingly, using iHm5-Val103 we identified a monoclonal antibody (moANCA518) from a patient with GPA that bound selectively to iHm5-Val103. Inhibition experiments using epitope-specific monoclonal antibodies and their antigen-binding fragments mapped the binding sites of moANCA518 and PR3-ANCAs (from patients displaying preferential binding to iHm5-Val103 over iPR3-Val103) to Epitope 3 on iHm5-Val103, a mutation-free epitope located far from the mutation sites in Epitope 5. These results demonstrate that the selective binding of moANCA518 (and likely the preferential binding of PR3-ANCAs from patients) to iHm5-Val103 is conferred by increased antigenicity of Epitope 3 on iHm5-Val103 caused by distal mutations, indicating that PR3-ANCAs bind to epitopes of a folded antigen conducive to allosteric effects of mutations—a previously unrecognized characteristic with implications for studying antibody-mediated autoimmune diseases and novel treatment approaches.

Sign in / Sign up

Export Citation Format

Share Document